The circadian clock is a major regulatory system that is involved a wide variety of physiological and behavioral processes in humans, and disruptions of circadian organization have been implicated in a variety of human health problems including those associated with insomnias, shift-work, jet-lag, aging, and certain affective disorders. The research proposed addresses fundamental questions in several areas related to animal circadian organization: What is the extent to which circadian systems modulate sensory input at the level of primary receptors? What are the consequences for behaviors that are dependent on these inputs? What is the output pathway(s) by which the circadian system regulates circadian rhythms in physiology and behavior? The questions will be tackled utilizing the olfactory system of an insect, the cockroach Leucophaea maderae, as a model system. Insect olfaction is an excellent model for these questions, both because of the existence of a solid foundation of information on insect olfaction and because of the critical importance of olfaction in host identification and feeding for insects that act as disease vectors. In addition, the cockroach is unique as an invertebrate model system for studies of circadian organization because, like mammals, photoreception for entrainment is exclusively retinal. The research program is conceptually based on the novel hypothesis that circadian clocks globally impose daily rhythmicity on the sensitivity of animal sensory systems at the level of the primary sensory neurons. The experiments are based on the specific hypothesis that there is a circadian rhythm of sensitivity of receptor neurons in the antennae and in olfactory behavior of the cockroach that is driven by a circadian pacemaker in the optic lobes of the brain. Further, it is suggested that the rhythmic modulation of octopamine levels is a strong candidate as a circadian signal that drives the rhythms in receptor sensitivity. The specific goals of the proposal are to establish, via long-term recording of individual tactile and olfactory receptor neurons, that the circadian clock does regulate sensitivity of primary sensory receptors, to demonstrate that the behavioral sensitivity to olfactory cues is regulated by the circadian system and to explore the consequences of regulation of the olfactory receptors on olfactory behavior, and to examine the role of octopamine in the regulatory pathways that impose rhythmicity on receptors and behavior .